Nitric oxide modulates Ca(2+) channels in dorsal root ganglion neurons innervating rat urinary bladder

J Neurophysiol. 2001 Jul;86(1):304-11. doi: 10.1152/jn.2001.86.1.304.


The effect of a nitric oxide (NO) donor on high-voltage-activated Ca(2+) channel currents (I(Ca)) was examined using the whole cell patch-clamp technique in L(6)-S(1) dorsal root ganglion (DRG) neurons innervating the urinary bladder. The neurons were labeled by axonal transport of a fluorescent dye, Fast Blue, injected into the bladder wall. Approximately 70% of bladder afferent neurons exhibited tetrodotoxin (TTX)-resistant action potentials (APs), and 93% of these neurons were sensitive to capsaicin, while the remaining neurons had TTX-sensitive spikes and were insensitive to capsaicin. The peak current density of nimodipine-sensitive L-type Ca(2+) channels activated by depolarizing pulses (0 mV) from a holding potential of -60 mV was greater in bladder afferent neurons with TTX-resistant APs (39.2 pA/pF) than in bladder afferent neurons with TTX-sensitive APs (28.9 pA/pF), while the current density of omega-conotoxin GVIA-sensitive N-type Ca(2+) channels was similar (43-45 pA/pF) in both types of neurons. In both types of neurons, the NO donor, S-nitroso-N-acetylpenicillamine (SNAP) (500 microM), reversibly reduced (23.4-26.6%) the amplitude of I(Ca) elicited by depolarizing pulses to 0 mV from a holding potential of -60 mV. SNAP-induced inhibition of I(Ca) was reduced by 90% in the presence of omega-conotoxin GVIA but was unaffected in the presence of nimodipine, indicating that NO-induced inhibition of I(Ca) is mainly confined to N-type Ca(2+) channels. Exposure of the neurons for 30 min to 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM), an inhibitor of NO-stimulated guanylyl cyclase, prevented the SNAP-induced reduction in I(Ca). Extracellular application of 8-bromo-cGMP (1 mM) mimicked the effects of NO donors by reducing the peak amplitude of I(Ca) (28.6% of reduction). Action potential configuration and firing frequency during depolarizing current pulses were not altered by the application of SNAP (500 microM) in bladder afferent neurons with TTX-resistant and -sensitive APs. These results indicate that NO acting via a cGMP signaling pathway can modulate N-type Ca(2+) channels in DRG neurons innervating the urinary bladder.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Animals
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / physiology
  • Calcium Channels, N-Type / physiology*
  • Capsaicin / pharmacology
  • Cyclic GMP / metabolism
  • Enzyme Inhibitors / pharmacology
  • Female
  • Ganglia, Spinal / cytology*
  • Nerve Fibers / drug effects
  • Nerve Fibers / metabolism
  • Nerve Fibers, Myelinated / drug effects
  • Nerve Fibers, Myelinated / metabolism
  • Neurons, Afferent / metabolism*
  • Neurons, Afferent / ultrastructure
  • Nimodipine / pharmacology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / pharmacology
  • Oxadiazoles / pharmacology
  • Penicillamine / analogs & derivatives
  • Penicillamine / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Tetrodotoxin / pharmacology
  • Urinary Bladder / innervation*
  • omega-Conotoxin GVIA / pharmacology


  • 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Calcium Channels, N-Type
  • Enzyme Inhibitors
  • Nitric Oxide Donors
  • Oxadiazoles
  • Quinoxalines
  • S-nitro-N-acetylpenicillamine
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Nitric Oxide
  • Tetrodotoxin
  • Nimodipine
  • omega-Conotoxin GVIA
  • Penicillamine
  • Cyclic GMP
  • Capsaicin